Skip to content

Extraintestinal Non Celiac Wheat Sensitivity

Extraintestinal Manifestations in Non Celiac Wheat Sensitivity

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT04769180
Enrollment
200
Registered
2021-02-24
Start date
2000-01-01
Completion date
2021-01-01
Last updated
2021-02-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-celiac Gluten Sensitivity

Keywords

Non-celiac Gluten Sensitivity, Celiac Disease, Irritable Bowel Syndrome

Brief summary

Non Celiac Gluten Sensitivity (NCGS), or, better, Non Celiac Wheat Sensitivity (NCWS), since it is not known the real pathogenetic component(s) of grain, is a syndrome characterized by a cohort of symptoms, both gastrointestinal and extraintestinal, related to the ingestion of gluten/wheat-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. In particular, the possibility of extraintestinal manifestations in this condition has been suggested by some reports. In most cases, they are characterized by vague symptoms, such as headache, 'foggy mind', fatigue, joint and muscle pain, leg or arm numbness (i.e., fibromyalgia-like symptoms), even if more specific complaints have been described. A possible neurological involvement has been underlined by NCWS association with gluten encephalopathy, gluten ataxia, and gluten peripheric neuropathy. NCWS patients may show even psychiatric diseases, such as anxiety, depression, and psychosis. Other described extraintestinal manifestations are dermatitis, (eczema or skin rash), gynecological disorders, and anemia. In addition, the association of NCWS with autoimmune diseases, such as autoimmune thyroiditis, and presence of anti-nuclear or other autoantibodies has been demonstrated, suggesting that, similarly to CD, NCWS might be considered as an immune system-related disease, and this aspect should be of relevance. In conclusion, the novelty of this matter has generated an expansion of literature data about the clinical features of the disease, with the unavoidable consequence that some reports are often based on low levels of evidence. The aims of the present study were to: a) retrospectively evaluate the prevalence and kind of extraintestinal symptoms in a large cohort of NCWS patients; b) to research for a possible relationship between the clinical, serological, genetic and histological characteristics of the NCWS patients and the number and kind of extraintestinal manifestations. As control groups, the researchers used CD and Irritable Bowel Syndrome (IBS) patients unrelated to NCWS or other food allergies/intolerances.

Detailed description

Non Celiac Gluten Sensitivity (NCGS), or, better, Non Celiac Wheat Sensitivity (NCWS), since it is not known the real pathogenetic component(s) of grain, is a syndrome characterized by a cohort of symptoms, both gastrointestinal and extraintestinal, related to the ingestion of gluten/wheat-containing food in subjects who are not affected by celiac disease (CD) or wheat allergy. In detail, NCWS is distinguished by symptoms that typically take place soon after gluten/wheat ingestion, withdraw with gluten/wheat exclusion, and relapse following gluten/wheat challenge (i.e., double-blinded placebo-controlled, DBPC, gluten/wheat challenge, used for diagnostic purpose) within hours or days. The gastrointestinal clinical picture of NCWS is a combination of irritable bowel syndrome (IBS)-like manifestations, such as abdominal pain, bloating, diarrhea, or constipation, or alternation of diarrhea and constipation, and dyspepsia like-symptoms, such as postprandial heaviness, early satiety, and epigastric pain or burning. However, the possibility of extraintestinal manifestations in this condition has been suggested by some reports. In most cases, they are characterized by vague symptoms, such as headache, 'foggy mind', fatigue, joint and muscle pain, leg or arm numbness (i.e., fibromyalgia-like symptoms), even if more specific complaints have been described. A possible neurological involvement has been underlined by NCWS association with gluten encephalopathy, gluten ataxia, and gluten peripheric neuropathy. NCWS patients may show even psychiatric diseases, such as anxiety, depression, and psychosis. Other described extraintestinal manifestations are dermatitis, (eczema or skin rash), gynecological disorders, and anemia. In addition, the association of NCWS with autoimmune diseases, such as autoimmune thyroiditis, and presence of anti-nuclear or other autoantibodies has been demonstrated, suggesting that, similarly to CD, NCWS might be considered as an immune system-related disease, and this aspect should be of relevance. In conclusion, the novelty of this matter has generated an expansion of literature data about the clinical features of the disease, with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples, with the inclusion of control groups, may be able to clearly establish whether the large information from the literature regarding extraintestinal NCWS manifestations could be supported by evidence-based agreements. Therefore, the aims of the present study were to: a) retrospectively evaluate the prevalence and kind of extraintestinal symptoms in a large cohort of NCWS patients, diagnosed by DBPC gluten/wheat challenge; b) to research for a possible relationship between the clinical, serological, genetic and histological characteristics of the NCWS patients and the number and kind of extraintestinal manifestations. As control groups, the researchers used CD and IBS patients unrelated to NCWS or other food allergies/intolerances.

Interventions

OTHEREvaluation of extraintestinal manifestations

The researchers evaluated the prevalence and kind of extraintestinal symptoms in NCWS patients and the possible relationship between the clinical, serological, genetic and histological characteristics of the NCWS patients and the number and kind of extraintestinal manifestations, using, as control groups, CD and IBS patients.

Sponsors

University of Palermo
Lead SponsorOTHER

Study design

Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

NCWS Inclusion Criteria: NCWS was diagnosed after CD or WA had been ruled out in all the studied patients according to the following criteria: * (1) negative serum assays for serum CD-anti-tissue transglutaminase (anti-tTG) immunoglobulin (Ig) A and anti-deamidated gliadin peptide (anti-DGP) IgG antibodies; (2) absence of intestinal villous atrophy, documented in all the patients carrying the DQ2 and/or the DQ8 HLA haplotypes (thus irrespective of CD-specific serum antibody negativity), evaluated when patients had a minimum intake of 100 g of wheat daily since at least 2 weeks; (3) negative IgE-mediated immune-allergy tests to wheat (skin prick tests and/or specific serum IgE detection); (4) resolution of symptoms on a standard elimination diet, without wheat, cow's milk, yeast, and other food(s) causing self-reported symptoms, followed by symptom reappearance on a DBPC wheat challenge. Additional inclusion criteria were: age older than 18 years, follow-up duration longer than 12 months after the initial diagnosis, and at least 2 outpatient visits during the follow-up period. NCWS

Exclusion criteria

* (1) positive anti-endomysial antibodies (EmA) in the culture medium of the duodenal biopsies, also in the case of normal villi/crypts ratio in the duodenal mucosa; (2) self-exclusion of wheat from the diet and refusal to reintroduce it before entering the study; (3) other previously diagnosed gastrointestinal disorders; (4) nervous system disease and/or major psychiatric disorder; (5) physical impairment limiting physical activity. CD Inclusion Criteria: * (1) positive serum anti-tTG and EmA IgA and IgG antibodies; (2) presence of intestinal villous atrophy. CD

Design outcomes

Primary

MeasureTime frameDescription
Evaluation of extraintestinal symptoms in NCWS patientsUp to 15 yearsEvaluation of systemic (malaise, fatigue), dermatological (eczema or skin rash), neurological (headache, 'foggy mind', gluten encephalopathy, gluten ataxia, gluten peripheric neuropathy, leg or arm numbness), psychiatric (anxiety, depression, psychosis), musculoskeletal (joint and muscle pain), gynaecological, and hematological (anemia) symptoms in NCWS patients.
Evaluation of extraintestinal symptoms in CD patientsUp to 15 yearsEvaluation of systemic (malaise, fatigue), dermatological (eczema or skin rash), neurological (headache, 'foggy mind', gluten encephalopathy, gluten ataxia, gluten peripheric neuropathy, leg or arm numbness), psychiatric (anxiety, depression, psychosis), musculoskeletal (joint and muscle pain), gynaecological, and hematological (anemia) symptoms in CD patients.
Evaluation of extraintestinal symptoms in IBS patients unrelated to NCWS or other food allergies/intolerances.Up to 15 yearsEvaluation of systemic (malaise, fatigue), dermatological (eczema or skin rash), neurological (headache, 'foggy mind', gluten encephalopathy, gluten ataxia, gluten peripheric neuropathy, leg or arm numbness), psychiatric (anxiety, depression, psychosis), musculoskeletal (joint and muscle pain), gynaecological, and hematological (anemia) symptoms in IBS patients unrelated to NCWS or other food allergies/intolerances.

Countries

Italy

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026